1. Field of the Invention
The present invention relates to the improved dosing of medication. Specifically, this invention improves the therapeutic effect of a central nervous system stimulant such as methylphenidate hydrochloride by delivering the medication over a predetermined period of time. In the present invention an initial immediate dose of the central nervous system stimulant is delivered followed by a second controlled dose of the medication from a single oral dosage form. The invention helps improve patient compliance and decreases the need for additional daily doses of the medication.
2. Description of the Related Art
Methylphenidate is a central nervous system stimulant used to treat Attention-Deficit Disorder (ADD) and Attention-Deficit Hyperactivity Disorder (ADHD), available commercially as, e.g. RITALIN SR®, CONCERTA™, METADATE™ CD capsules and METEADATE™ ER Tablets. The beneficial results seen by clinicians in the treatment of ADD and ADHD has resulted in widespread use of methylphenidate in more than two million patients annually. Methylphenidate exists in four separate optical isomers, l-threo, d-erythro, d-threo and l-erythro, with the threo pair of enantiomers (racemate) of methylphenidate hydrochloride generally administered for the treatment of ADD and ADHD. Methylphenidate hydrochloride is a mild central nervous system stimulant with pharmacological properties similar to that of amphetamines. The side effects which are associated with the use of methylphenidate include anorexia, weight loss, insomnia, dizziness and dysphoria. Methylphenidate is categorized by the DEA as a Schedule II controlled substance because it produces a euphoric effect when administered intravenously or through inhalation or ingestion, and thus carries a high potential for abuse.
Numerous sustained release formulations of methylphenidate which provide for a slow release of the medication over a predetermined period of time have been developed and some of these formulations are described in U.S. Pat. Nos. 6,340,476, 6,344,215, 6,372,254, 6,368,626, 5,837,284 and 6,034,101, incorporated herein by reference. However, when methylphenidate is delivered at a steady state over a sustained period of time, acute tolerance often develops. The undesirable clinical effects of steady state sustained release formulations are overcome by multiple dosing whereby the intensity of the therapeutic effects of the methylphenidate can be maintained.
The sustained release tablet form of methylphenidate hydrochloride described in U.S. Pat. No. 6,034,101 and incorporated herein by reference, comprises a sustained release tablet that provides an ascending dose of the drug. This does not model the multiple dose administration of immediate release methylphenidate hydrochloride tablets. Controlled release of the medication is achieved by a hydrogel matrix.
The sustained release formulation of methylphenidate described in U.S. Pat. No. 5,837,284 and incorporated herein by reference, is made up of two groups of particles. One group provides a substantially immediate dose of methylphenidate drug, the other supplies a dose of methylphenidate delayed by about 2 to 7 hours.
Sustained release formulations of methylphenidate have been developed, which provide for the slow release of the drug over the course of the day. However it has been observed that peak plasma concentrations of the drug are lower when sustained release formulations are used. Studies have shown that sustained release formulations of methylphenidate have been shown to have lower efficacy than conventional dosage forms.
Although the prior art controlled release formulation provide steady increases in the blood level of methylphenidate hydrochloride, they may be less than desirable because their delivery rates do not mimic the plasma profile of multiple dose regimens known to prevent tolerance.
To overcome the previously mentioned problems with sustained delivery of methylphenidate, the present invention provides the needed delivery system whereby the drug can be administered in a single dose and provide the needed delivery rate so that tolerance to its effects will not develop. Furthermore, a single effective daily dose will eliminate the risk of theft or loss of the second dose and increase the medications overall therapeutic value.